Li, WenluMandeville, Emiri TDurán-Laforet, VioletaFukuda, NoritoYu, ZhanyangZheng, YiHeld, AaronPark, Ji-HyunNakano, TakafumiTanaka, MasayoshiShi, JingfeiEsposito, ElgaNiu, WantingXing, ChanghongHayakawa, KazuhideLizasoain, Ignaciovan Leyen, KlausJi, XunmingWainger, Brian JMoro, Maria ALo, Eng H2024-05-092024-05-092022-12-19Nat Commun. 2022 Dec 19;13(1):7812.http://hdl.handle.net/20.500.12105/19324The concept of the neurovascular unit emphasizes the importance of cell-cell signaling between neural, glial, and vascular compartments. In neurogenesis, for example, brain endothelial cells play a key role by supplying trophic support to neural progenitors. Here, we describe a surprising phenomenon where brain endothelial cells may release trans-differentiation signals that convert astrocytes into neural progenitor cells in male mice after stroke. After oxygen-glucose deprivation, brain endothelial cells release microvesicles containing pro-neural factor Ascl1 that enter into astrocytes to induce their trans-differentiation into neural progenitors. In mouse models of focal cerebral ischemia, Ascl1 is upregulated in endothelium prior to astrocytic conversion into neural progenitor cells. Injecting brain endothelial-derived microvesicles amplifies the process of astrocyte trans-differentiation. Endothelial-specific overexpression of Ascl1 increases the local conversion of astrocytes into neural progenitors and improves behavioral recovery. Our findings describe an unexpected vascular-regulated mechanism of neuroplasticity that may open up therapeutic opportunities for improving outcomes after stroke.engVoRhttp://creativecommons.org/licenses/by/4.0/StrokeNeural Stem CellsMaleMiceAnimalsAstrocytesEndothelial CellsCells, CulturedCell TransdifferentiationAtribución 4.0 Internacional36535938131781210.1038/s41467-022-35498-62041-1723Nature communicationsopen access